Critical role of TLR4 in uncovering the increased rewarding effects of cocaine and ethanol induced by social defeat in male mice

Autor: S. MONTAGUD-ROMERO, M. REGUILON, M. PASCUAL, M. BLANCO-GANDIA, C. GUERRI, J. MINARRO, M. RODRIGUEZ-ARIAS
Rok vydání: 2021
Předmět:
Zdroj: NEUROPHARMACOLOGY
r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)
instname
r-CIPF: Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)
Centro de Investigación Principe Felipe (CIPF)
ISSN: 0028-3908
Popis: Background: Substance use disorders and social stress are currently associated with changes in the immune system response by which they induce a proinflammator y state in neurons and glial cells that eventually modulates the reward system. Aims: The aim of the present work was to assess the role of the immune TLR4 (Toll-like receptors 4) and its signaling response in the increased contextual reinforcing effects of cocaine and reinforcing effects of ethanol (EtOH) induced by social defeat (SD) stress. Methods: Adult male C57BL/6 J wild-type (WT) mice and mice deficient in TLR4 (TLR4-KO) were assigned to experimental groups according to stress condition (exploration or SD). Three weeks after the last SD, conditioned place preference (CPP) was induced by a subthreshol d cocaine dose (1 mg/kg), while another set underwent EtOH 6% operant self-administration (SA). Several inflammator y molecules were analyzed in the hippocampus and the striatum. Results: SD induced higher vulnerability to the conditioned rewarding effects of cocaine only in defeated WT mice. Similarly, defeated WT mice exhibited higher 6% EtOH consumption, an effect that was not observed in the defeated TLR4-KO group. However, the motivation to obtain the drug was observed in both genotypes of defeated animals. Notably, a significant upregulation of the protein proinflammator y markers NFkBp-p65, IL-1 beta, IL-17 A and COX-2 were observed only in the defeated WT mice, but not in their defeated TLR4-KO counterparts. Conclusions: These results suggest that TLR4 receptors mediate the neuroinflammator y response underlying the increase in the rewarding effects of cocaine and EtOH induced by social stress.
Databáze: OpenAIRE
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